The ENTRY-DM Doctoral Network, funded under the prestigious Marie Skłodowska-Curie Actions – Doctoral Networks (MSCA-DN) programme, is offering 14 fully funded PhD positions across leading European institutions. 

ENTRY-DM is an ambitious interdisciplinary and intersectoral training programme that will equip the next generation of researchers with the expertise to develop novel oligonucleotide-based therapies for myotonic dystrophy. This programme brings together leading academic institutions, innovative biotech companies, and patient advocacy groups, forming a unique collaborative environment for doctoral training at the intersection of fundamental science, translational medicine, and clinical application.

Myotonic dystrophy (DM) is the most common inherited muscular dystrophy in adults. It is a complex multi-systemic disorder, impacting not only skeletal and cardiac muscle but also the nervous system, among others. Despite recent advances in understanding the genetic and molecular mechanisms of DM, no effective treatment is currently available. The use of antisense oligonucleotides (ASOs) to counteract the disease-causing mutant RNA has faced delivery challenges and insufficient therapeutic efficacy. The development of clinically viable RNA-targeted therapeutics requires overcoming key scientific and technological hurdles, including poor ASO biodistribution, limited penetration of critical tissues, and the lack of reliable biomarkers to monitor disease progression and treatment response.

ENTRY-DM aims to transform the therapeutic landscape for DM by training a new generation of creative PhD researchers in a structured, interdisciplinary research programme. The project will focus on three major research objectives: (1) development of innovative disease models and exploring disease mechanisms, (2) optimising ASO-based therapies, and (3) defining clinical biomarkers for clinical trials. PhD researchers will investigate genotype-phenotype correlations and RNA dynamics, leveraging cutting-edge genomics, bioinformatics, stem cell research, bioengineering of innovative 3D disease models, medicine chemistry, advanced imaging techniques, as well as neuropsychology approaches and clinical applications, in a truly multidisciplinary project.

To achieve these goals, ENTRY-DM has assembled a consortium of leading European research institutions and biotech companies, providing a truly international and intersectoral research environment. The 9 academic and 2 non-academic beneficiaries include renowned universities and research centres in France, Spain, Italy, the Netherlands, Germany, and Poland, complemented by 13 associated partners, including patient organisations and biotech companies. Each PhD candidate will be hosted in a dynamic, multi-disciplinary and international setting, benefiting from inter-sectoral secondments, world-class supervision, and specialised training in advanced research techniques, innovation, and career development.

Join ENTRY-DM and contribute to the next wave of RNA-based therapeutics for myotonic dystrophy, a field at the cutting edge of precision medicine and molecular therapies. Be part of a transformative research network that will shape the future of rare disease treatment.

Beneficiaries & Research Institutions

The ENTRY-DM consortium includes 9 academic and 2 non-academic beneficiaries from 6 European countries, along with leading associated partners from academia, industry, and patient organisations. PhD positions are available at the following institutions:

• Inserm (Paris, France) – 2 positions
• Universitat de València (Valencia, Spain) – 2 positions
• Institut de Bioenginyeria de Catalunya (Barcelona, Spain) – 1 position
• Università di Roma Tor Vergata (Rome, Italy) – 1 position
• Radboud University Medical Centre (Nijmegen, The Netherlands) – 2 positions
• Ludwig-Maximilians-Universität München (Munich, Germany) – 1 position
• Adam Mickiewicz University in Poznań (Poznan, Poland) – 1 position
• Centre d’Etudes des Cellules Souches (Evry, France) – 1 position
• Genartis (Genova, Italy) – 1 position
• Université Paris Cité (Paris, France) – 1 position
• Consejo Superior de Investigaciones Científicas (Barcelona, Spain) – 1 position
   

Project description:

The main objective of this project is to develop a therapeutic strategy of DM1 to eliminate the fragment containing CUGexp from mutant mRNA of DMPK using ASO. The CUGexp is localized within the terminal exon of the DMPK gene, which undergoes alternative splicing. Downstream of the CUGexp in exon 15 there is a cryptic 3′ splice acceptor site, which defines a new terminal exon termed exon 16. The use of 3′ splice acceptor results in the excision of a large 5′ part portion of exon 15, including the CUG-repeat region. To identify ASO molecules that induce efficient skipping of the CUGexp-containing mRNA fragment, DC8 will screen a library of at least 20 oligonucleotides targeting intronic and exonic regions potentially regulating efficiency of exon 15 exclusion. Moreover DC8 will test ASO targeting directly CCUGexp in mutant RNA in DM2 cells. DC8 will use different chemistries of modified oligonucleotides (2’-LNA, -MOE, -O-Me) and first test them in well characterized DM1- and DM2-patients derived fibroblasts, through the assessment of splicing correction and reduction of CUGexp, CCUGexp foci formation.  Next, the best oligonucleotides after chemical diversification, that exhibit better bioavailability in vivo (secondment with UO), will be tested in DMSXL mice, a transgenic DM1 model developed by INSERM and in iPSCs of DM1 and DM2 patients (secondment with Centre d’Etudes des Cellules Souches). Using these mouse and cell models available in our network, DC8 will test molecular and physiological biomarkers of disease (e.g., nuclear CUGexp or CCUGexp foci formation, MBNL sequestration, efficiency of exon 15 skipping, correction of alternative splicing and muscle function).

Candidate’s Profile:

We are looking for highly motivated and ambitious DC with a strong background in molecular and cellular biology. A strong interest in development of RNA-based therapeutics and biomarker discovery is essential. Applicants should hold a Master’s degree (or equivalent) in Molecular Life Sciences, Physiology, Biomedical Sciences, or a related discipline. Hands-on experience in key molecular biology techniques, including PCR, RT-PCR, and cell culture, is required. Prior experience with transcriptomics, as well as in vitro and/or in vivodisease models is highly desirable.

The ideal candidate will possess strong analytical and problem-solving skills, a high level of scientific curiosity, and a commitment to advancing therapeutic research. Excellent communication and teamwork abilities are required to collaborate effectively within a multidisciplinary and international research environment. Proficiency in English is mandatory.

Doctoral candidates will spend time on secondment during their 36 month employment contracts. Anticipated secondments for this position are: 

(1) Centre d’Etudes des Cellules Souches, Cécile Martinat (Evry, France). Testing candidate compounds on the disease biomarkers of hiPSC-derived cell modelsof DM1 and/or DM2. (2) The University of Oxford, Miguel. Varela (Oxford, United Kingdom). Evaluation of the toxicology and biodistribution of selected ASO.

Application Process

Interested candidates should submit a single PDF document to Krzysztof Sobczak (krzysztof.sobczak@amu.edu.pl) and recruitment.entrydm@gmail.com, named with your full name.

1. A detailed CV (maximum two pages), specifying educational background (name of university/universities, year degree(s) obtained, title(s) of degree(s)), qualifications, work experience, skills, research interests, list of publications (if any) and the names and contact details of two referees.
2. A motivation letter (maximum two pages), describing the candidate’s interest in the network, previous research experience, and current research interest outlining the fit to the desired PhD Project. If you are planning to apply to more than one position in the network, please limit your applications to three positions maximum (from DC1 to DC14) and please provide a separate document detailing which positions you have applied for. 
3. Copy of passport or National Identify Card.
4. Copies of academic certificates (BSc, MSc, and any other relevant diplomas), translated into English, including expected final grade and date.
5. Proof of English proficiency, demonstrated by IELTS, TOEFL, or a university certification confirming that the degree or MSc thesis was conducted in English.
6. Two recommendation letters (maximum 1 page each).

Only documents in English will be accepted.

Applications failing to include the requested documentation, who do not indicate the preferred projects or do not meet the eligibility criteria, will not be considered.

For more information about the project: https://www.institut-myologie.org/2025/02/10/entry-dm-un-reseau-europeen-pour-former-une-nouvelle-generation-de-jeunes-chercheurs-sur-la-dm1-entretien-avec-mario-gomes-pereira/